The proposed research will explore further the usefulness of an in vitro model for elucidating mechanisms regulating human IgE synthesis through studies on 1) the nature of the human blood cell producing IgE, 2) its responsiveness to as yet untried polyclonal B cell activators, 3) the number of FcEpsilon receptor-bearing T cells in atopic and normal human blood and their distribution within the suppressor and helper subpopulations, 4) IgE binding factor production by atopic and normal T cells, 5) the response of human B cells producing IgE to these factors, 6) the effects of various pharmacologic agents on human IgE production, and 7) the effects of tolerogenic conjugates of allergen with monomethoxypolyethylene glycol on human MNC IgE synthesis. The question of whether IgE binding factors from human blood T cells can augment or suppress IgE synthesis in vitro will be examined and, if so, whether the binding factors from atopic T cells are different in their functional capacities from those from normal T cells. The methodology to be employed includes 1) our originally developed and time-proven method for detecting IgE synthesis in vitro, 2) "panning" techniques with monoclonal antibodies to B ant T cell surface antigens to purify subpopulations of lymphocytes, 3) rosetting with ox erythrocytes coated with IgE to detect FcEpsilonR+ cells, 4) inhibition of binding of IgE to an Fc R+ B cell line to detect IgE binding factors, and 5) radioimmunoassays for total and specific IgE. The long term objective of this research is to gain information as to how the human IgE response might be manipulated so that it can be abrogated in disease states caused or accompanied by excessive IgE antibody production.